Comparison of Short-term and Three-year Oncological Outcomes Between Robotic and Laparoscopic Gastrectomy for Gastric Cancer: A Large Multicenter Cohort Study.

OBJECTIVE: To compare the short-term and long-term outcomes between robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. BACKGROUND: The clinical outcomes of RG over LG have not yet been effectively demonstrated. METHODS: This retrospective cohort study included 3599 patients with gastric cancer who underwent radical gastrectomy at eight high-volume hospitals in China from January 2015 to June 2019. Propensity score matching was performed between patients who received RG and LG. The primary end point was 3-year disease-free survival (DFS). RESULTS: After 1:1 propensity score matching, 1034 pairs of patients were enrolled in a balanced cohort for further analysis. The 3-year DFS in the RG and LG was 83.7% and 83.1% ( P =0.745), respectively, and the 3-year overall survival was 85.2% and 84.4%, respectively ( P =0.647). During 3 years of follow-up, 154 patients in the RG and LG groups relapsed (cumulative incidence of recurrence: 15.0% vs 15.0%, P =0.988). There was no significant difference in the recurrence sites between the 2 groups (all P >0.05). Sensitivity analysis showed that RG had comparable 3-year DFS (77.4% vs 76.7%, P =0.745) and overall survival (79.7% vs 78.4%, P =0.577) to LG in patients with advanced (pathologic T2-4a) disease, and the recurrence pattern within 3 years was also similar between the 2 groups (all P >0.05). RG had less intraoperative blood loss, lower conversion rate, and shorter hospital stays than LG (all P >0.05). CONCLUSIONS: For resectable gastric cancer, including advanced cases, RG is a safe approach with comparable 3-year oncological outcomes to LG when performed by experienced surgeons.

Robotic natural orifice specimen extraction surgery versus robotic transabdominal specimen extraction surgery for early-stage rectal cancer: a multicenter propensity score-matched analysis (in China).

BACKGROUND: Despite the global increase in the adoption of robotic natural orifice specimen extraction surgery (R-NOSES), its advantages over robotic transabdominal specimen extraction surgery (R-TSES) for treating early-stage rectal cancer remain debated. There is scant nationwide, multicenter studies comparing the surgical quality and short-term outcomes between R-NOSES and R-TSES for this condition. OBJECTIVE: This retrospective cohort study was conducted nationally across multiple centers to compare the surgical quality and short-term outcomes between R-NOSES and R-TSES in early-stage rectal cancer. DESIGN: Multicenter retrospective cohort trial. SETTING: Eight experienced surgeons from 8 high-volume Chinese colorectal cancer treatment centers. PATIENTS: The study included 1086 patients who underwent R-NOSES or R-TSES from October 2015 to November 2023 at the 8 centers. Inclusion criteria were: (1) histologically confirmed rectal adenocarcinoma; (2) robotic total mesorectal excision; (3) postoperative pathological staging of TisN0M0 or T1-2N0M0; (4) availability of complete surgical and postoperative follow-up data. Patients were matched 1:1 in the R-NOSES and R-TSES groups using the propensity score matching (PSM) technique. RESULTS: After PSM, 318 matched pairs with well-balanced patient characteristics were identified. The operation time for the R-NOSES group was significantly longer than that for the R-TSES group [140 min (125-170 min) vs. 140 min (120-160 min), P = 0.032]. Conversely, the times to first flatus and initial oral intake in the R-NOSES group were significantly shorter than those in the R-TSES group [48 h (41-56 h) vs. 48 h (44-62 h), P = 0.049 and 77 h (72-94 h) vs. 82 h (72-96 h), P = 0.008], respectively. Additionally, the length of postoperative hospital stay was shorter in the R-NOSES group compared with the R-TSES group [7 day (7-9 day) vs. 8 day (7-9 day), P = 0.005]. The overall postoperative complication rates were similar between the groups (10.7% in the R-NOSES group vs. 11.9% in the R-TSES group, P = 0.617). However, the R-NOSES group had a lower incidence of wound complications compared to the R-TSES group (0.0% vs. 2.2%, P = 0.015). Regarding surgical stress response, the R-NOSES group showed superior outcomes. Additionally, patients in the R-NOSES group required fewer additional analgesics on postoperative days 1, 3, and 5 and reported lower pain scores compared to the R-TSES group. The body image scale (BIS) and cosmetic scale (CS) scores were also significantly higher in the R-NOSES group. Furthermore, the R-NOSES group demonstrated significantly better outcomes in functional dimensions such as physical, role, emotional, social, and cognitive functioning, and in symptoms like fatigue and pain, when compared to the R-TSES group. LIMITATIONS: It is imperative to ensure the safe and standardized implementation of R-NOSES through the establishment of a uniform training protocol. CONCLUSIONS: These results affirm that R-NOSES is a safe and effective treatment for early-stage rectal cancer when meticulously executed by skilled surgeons.

Study of the Structure and Bioactivity of Polysaccharides from Different Parts of Stemona tuberosa Lour.

The polysaccharides from Stemona tuberosa Lour, a kind of plant used in Chinese herbal medicine, have various pharmacological activities, such as anti-inflammatory and antioxidant properties. However, the effects of the extraction methods and the activity of polysaccharides from different parts are still unknown. Therefore, this study aimed to evaluate the effects of different extraction methods on the yields, chemical compositions, and bioactivity of polysaccharides extracted from different parts of Stemona tuberosa Lour. Six polysaccharides were extracted from the leaves, roots, and stems of Stemona tuberosa Lour through the use of hot water (i.e., SPS-L1, SPS-R1, and SPS-S1) and an ultrasound-assisted method (i.e., SPS-L2, SPS-R2, and SPS-S2). The results showed that the physicochemical properties, structural properties, and biological activity of the polysaccharides varied with the extraction methods and parts. SPS-R1 and SPS-R2 had higher extraction yields and total sugar contents than those of the other SPSs (SPS-L1, SPS-L2, SPS-S1, and SPS-S2). SPS-L1 had favorable antioxidant activity and the ability to downregulate MUC5AC expression. An investigation of the anti-inflammatory properties showed that SPS-R1 and SPS-R2 had greater anti-inflammatory activities, while SPS-R2 demonstrated the strongest anti-inflammatory potential. The results of this study indicated that SPS-L1 and SPS-L2, which were extracted from non-medicinal parts, may serve as potent natural antioxidants, but further study is necessary to explore their potential applications in the treatment of diseases. The positive anti-inflammatory effects of SPS-R1 and SPS-R2 in the roots may be further exploited in drugs for the treatment of inflammation.

Two Green Protocols for Halogenative Semipinacol Rearrangement.

Semipinacol rearrangement is a special type of Wagner-Meerwein rearrangement that involves carbocation 1,2-rearrangement to provide carbonyl compounds with an α-quaternary carbon center. It has been strategically used for natural product synthesis and construction of highly congested quaternary carbons. Herein, we report a safe and green protocol that uses oxone/halide and Fenton bromide to achieve halogenative semipinacol rearrangement. The key feature of this method is the green in situ generation of reactive halogenating species from oxidation of halide with oxone or H2O2, which produces a nontoxic byproduct (potassium sulfate or water). Easy operation (insensitive to air and moisture) at room temperature without using special equipment adds additional advantage over previous methods.

Plasmodium-Resistant Indole Diterpenoid Biosynthesis Gene Cluster Derived from Aspergillus oryzae Was Activated by Exogenous P450 Gene Ast B.

Synthetic biology is an effective way to activate silent biosynthetic gene clusters. Five new indole diterpenoids (1, 2, 5, 9, and 10), together with 10 known derivatives (3, 4, 6-8, and 11-15) were activated from Aspergillus oryzae transformants by an exogenous P450 gene Ast B and obtained under the guidance of molecular networking. Their planar structures were determined by NMR and HR-ESI-MS. The absolute configuration of compound 1 was determined by single crystal X-ray diffraction, and those of compounds 2, 5 , 9, and 10 were confirmed by comparing the observed ECD with the calculated ECD. HPLC analysis suggested that the BGCs of indole diterpenoids in A. oryzae were activated by exogenous P450 gene Ast B. Compounds 1-4, 7, 8, and 11 displayed strong activity against chloroquine-sensitive plasmodium strain P.f.3D7 with IC50 values ranging from 0.84 to 2.9 µM. It is the first report that indole diterpenoids have potential antimalarial activity. The structure-activity relationship study showed that the linear indole diterpenoids contribute significantly to the antiparasite activity. Molecular docking studies showed that 1 and positive control chloroquine were at the center of the active pocket of PfHsp90, while 11 was far from the active site.

Environmentally Benign and User-Friendly In Situ Generation of Nitrile Imines from Hydrazones for 1,3-Dipolar Cycloaddition.

Nitrile imines are highly reactive and versatile dipoles and conventionally generated in situ from unstable hydrazonyl halides under basic conditions. Herein, we report the first green and user-friendly protocol for in situ generation of nitrile imines from Oxone-KBr oxidation of hydrazones and base-promoted dehydrobromination. The nitrile imines were demonstrated for 1,3-dipolar cycloaddition with various dipolarophiles, including alkene and alkyne groups. With its green nature, ease of operation, and air and moisture tolerance, we expect our method will find wide applications in organic synthesis.

Antiplasmodial Asperterpenoids from Two Aspergillus oryzae Transformants with Heterologous Expression of Sesterterpene Genes.

The synthetic biology approach enables efficient and directional mining of target compounds during drug discovery. Ten new asperterpenoids (6-15) and five known analogues (1-5), possessing a rare 5/7/3/6/5 skeleton, were obtained from two Aspergillus oryzae transformants with heterologous expression of a terpene cyclase gene AstC with one or two P450 genes AstB/A under the guidance of molecular networking. Their planar structures were determined by 1D and 2D NMR and HR-ESI-MS. The absolute configurations of compounds 6 and 9-13 were determined by single crystal X-ray diffraction, and those of compounds 7-8 and 14-15 were compared with the ECD of known compounds. Seven of all the compounds are the first asperterpenoid oxidation products at C-17 or at C-25. In bioassay, compounds 1-2, 4-5, and 6-8 displayed moderate to strong eliminating activities against chloroquine-sensitive strain (P.f.3D7) with EC50 values ranging from 2.1 to 19.3 µM. The structure-activity relationship (SAR) was discussed, which showed that substituents at C-3, C-11, C-17, C-18, and C-23 of asperterpenoids significantly affected anti-plasma parasite activity.

The safety and efficacy of laparoscopic surgery versus laparoscopic NOSE for sigmoid and rectal cancer.

BACKGROUND: Laparoscopic surgery with natural orifice specimen extraction (La-NOSE) is being performed more frequently for the minimally invasive management of sigmoid and rectal cancer. The objective of this meta-analysis was to compare the clinical and oncological safety and efficacy of La-NOSE versus conventional laparoscopy (CL). METHODS: A search of the PubMed, Web of Science, and Cochrane databases was performed for studies that compared clinical or oncological outcomes of conventional laparoscopic resection using NOSE with conventional laparoscopic resection for sigmoid and rectal cancer. RESULTS: Compared with CL group, the length of hospital stay and the pain score on the first day were shorter in the La-Nose group. The La-NOSE group had a lower incidence of total perioperative complications (OR 0.46; 95% CI [0.32 to 0.66]; I2 = 0%; P < 0.0001) and a lower incidence of surgical site infections (SSIs) (OR 0.11; 95% CI [0.04 to 0.29]; I2 = 0%; P < 0.0001) than the CL group, while the anastomotic leakage showed no significant difference between the La-Nose group and the CL group (P = 0.19). 5-year disease-free survival (DFS) and 5-year overall survival (OS) were no significant difference between the La-Nose group and the CL group (P = 0.43, P = 0.40, respectively). CONCLUSIONS: La-NOSE can achieve oncological and surgical safety comparable to that of CL for patients with sigmoid and rectal cancer. La-NOSE in patients was associated with a shorter hospital stay, shorter time to first flatus or defecation, less postoperative pain, and fewer surgical site infections (SSIs) and total perioperative complications. In general, the operative time in La-NOSE was longer than that in CL. The long-term oncological efficacy of La-NOSE seems to be equivalent to that of CL.

1,5-Allyl Shift by a Sequential Achmatowicz/Oxonia-Cope/Retro-Achmatowicz Rearrangement.

1,3-Allyl and 1,2-allyl shifts through [3,3]- and [2,3]-sigmatropic rearrangements are well-established and widely used in organic synthesis. In contrast, 1,5-allyl shift through related [3,5]-sigmatropic rearrangement is unknown because [3,5]-sigmatropic rearrangement is thermally Woodward-Hoffmann forbidden. Herein, we report an unexpected discovery of a formal 1,5-allyl shift of allyl furfuryl alcohol through a 2-step sequential rearrangement. Mechanistically, this formal 1,5-allyl shift is achieved through a sequential ring expansion/contraction rearrangement: 1) Achmatowicz rearrangement (ring expansion), and 2) cascade oxonia-Cope rearrangement/retro-Achmatowicz rearrangement (ring contraction). This new 1,5-allyl shift method is demonstrated with >20 examples and expected to find applications in organic synthesis and materials chemistry.

Inhibitor of apoptosis-stimulating p53 protein protects against inflammatory bowel disease in mice models by inhibiting the nuclear factor kappa B signaling.

Drugs and therapies available for the treatment of inflammatory bowel disease (IBD) are not satisfactory. Our previous study has established the inhibitor of apoptosis-stimulating p53 protein (iASPP) as an oncogenic regulator in colorectal cancer by forming a regulatory axis or feedback loop with miR-124, p53, or p63. As iASPP could target and inhibit nuclear factor kappa B (NF-κB) activation, in this study the role and mechanism of iASPP in IBD was investigated. The aberrant up-regulation of iASPP in IBD was subsequently confirmed, based on online data sets, clinical sample examinations and 2,4,6-trinitrobenzene sulfonic acid (TNBS)- and dextran sulfate sodium (DSS)-induced colitis mice models. TNBS or DSS stimulation successfully induced colon shortness, body weight loss, mice colon oxidative stress and inflammation. In both types of colitis mice models, iASPP over-expression improved, whereas iASPP knockdown aggravated TNBS or DSS stimulation-caused colon shortness, body weight loss and mice colon oxidative stress and inflammation. Meanwhile, in both types of colitis mice models, iASPP over-expression inhibited p65 phosphorylation and decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, C-X-C motif chemokine ligand (CXCL)1 and CXCL2 in mice colons, whereas iASPP knockdown exerted opposite effects.

6-Shogaol from ginger shows anti-tumor effect in cervical carcinoma via PI3K/Akt/mTOR pathway.

PURPOSE: 6-Shogaol, an active phenolic compound from ginger (Zingiber officinale), can inhibit the growth of a variety of human cancer cells. Nevertheless, its underlying molecular mechanisms in cervical cancer remain unclear. In this study, we systematically examine the inhibitory effect of 6-shogaol on cervical cancer in vitro and in vivo. METHODS: Cell proliferation was assessed by CCK8 assay and colony formation assay in HeLa and SiHa cells. We analyzed cell cycle and apoptosis through flow cytometry. GFP-LC3 puncta and transmission electron microscopy were used to observe autophagic bodies. Wound-healing assay and transwell assay were used for evaluating the migration of cells. Western blot was applied to detect protein expression levels. RESULTS: 6-Shogaol could suppress cell proliferation and migration, cause cell cycle arrest in the G2/M phase in HeLa and SiHa cells. Moreover, 6-shogaol triggered the apoptosis process through the mitochondrial pathway by downregulating the expression levels of p-PI3K, p-Akt and p-mTOR. Further research indicated that the induction of apoptosis by 6-shogaol was remarkably decreased after the treatment of ROS scavenger and PI3K agonist. Additionally, 6-shogaol increased the number of LC3-positive puncta and autophagic bodies per cell in both HeLa and SiHa cells. Pretreatment of cells with Bafilomycin A1, an autophagy inhibitor, accelerated 6-shogaol mediated cell apoptosis, suggesting that induction of autophagy by 6-shogaol is suppressive to apoptosis. Furthermore, in vivo data revealed that 6-shogaol significantly inhibited tumor growth and cell proliferation in tumor tissues. CONCLUSION: These findings suggested that 6-shogaol could be developed as a functional food ingredient, which is potentially used as therapeutic agents for patients with cervical cancer.

Robotic colorectal cancer surgery in China: a nationwide retrospective observational study.

BACKGROUND: Robotic colorectal cancer surgery is widely accepted and applied. However, there is still no objective and comprehensive assessment on the data of nationwide multicenter series. METHOD: A total of 28 medical centers in Mainland China participated in this nationwide retrospective observational study. From the first case performed in each center to the last until December 2017, patients with robotic resection for primary tumor and pathologically confirmed colorectal adenocarcinoma were consecutively enrolled. Clinical, pathological and follow-up data were collected and analyzed. RESULTS: A total of 5389 eligible patients were finally enrolled in this study, composing 72.2% of the total robotic colorectal surgery volume of Mainland China in the same period. For resections of one bowel segment of primary tumor, the postoperative mortality rate was 0.08% (4/5063 cases), and the postoperative complication rate (Clavien-Dindo grade II or higher) was 8.6% (434/5063 cases). For multiple resections, the postoperative mortality rate was 0.6% (2/326 cases), and the postoperative complication rate was 16.3% (53/326 cases). Out of 2956 patients receiving sphincter-preserving surgery in only primary resection, 130 (4.4%) patients had anastomotic leakage. Traditional low anterior resection (tumor at middle rectum) (OR 2.384, P < 0.001), traditional low anterior resection (tumor at low rectum) (OR 1.968, P = 0.017) and intersphincteric resection (OR 5.468, P = 0.006) were significant independent risk factors for anastomotic leakage. Female gender (OR 0.557, P = 0.005), age ≥ 60 years (OR 0.684, P = 0.040), and preventive stoma (OR 0.496, P = 0.043) were significant independent protective factors. Body mass index, preoperative chemotherapy/radiotherapy, tumor size, and TNM stage did not independently affect the occurrence of anastomotic leakage. CONCLUSION: Robotic colorectal cancer surgery was safe and reliable and might have advantages in patients at high risk of anastomotic leakage.

Different dosages of valaciclovir for the treatment of herpes zoster in adults: A randomized clinical study.

WHAT IS KNOWN AND OBJECTIVE: The dosages of valaciclovir used for herpes zoster treatment recommended by Chinese pharmaceutical companies can differ considerably from those reported in the literature. This randomized clinical study compares the efficacy and safety of different oral valaciclovir doses for the treatment of herpes zoster in adults. METHODS: A total of 214 patients with herpes zoster were enrolled and randomized into two groups according to age: 98 patients in the 18-44-year group (younger patients) and 116 patients in the 45-74-year group (middle-aged and elderly patients). Patients in the two age groups were then prescribed different doses of valaciclovir. The high-dose group was administered 900 mg of valaciclovir, three times daily for 10 days, whereas the low-dose group was administered 300 mg of valaciclovir, two times daily for 10 days. The efficacy and side effects of these regimens were recorded on days 6, 11 and 30. RESULTS: In total, 207 (of 214 enrolled) patients completed the study. Of the seven patients who discontinued the study, five discontinued because their follow-up time was not fixed and two withdrew after moving to other cities. At the 11th day after treatment, the clinical effect of high-dose valaciclovir groups were significantly better than that of the low-dose valaciclovir groups in middle-aged and elderly patients (p < 0.05). The difference in visual analog scale (VAS) pain scores between the two dose groups was statistically significant in middle-aged and elderly patients at the 6th day(p < 0.05), whereas there was no difference in younger patients (p > 0.05). The VAS scores were significantly lower in high-dose group than in low-dose group at day 11 in both groups of patients(p < 0.05).There was no statistically significant difference in the time to skin scab improvement between the two different dose groups in younger patients (p > 0.05). Among middle-aged and elderly patients, the incidence of postherpetic neuralgia (PHN) was significantly lower in the high-dose group than in the low-dose group (p < 0.05). The difference in the incidence of adverse reactions between the high-dose and low-dose groups was not statistically significant (p > 0.05). Overall, the main side effect was headache. WHAT IS NEW AND CONCLUSION: The present study indicates that early treatment with high-dose valaciclovir can significantly reduce pain in patients, especially in elderly patients, in whom it can also reduce the incidence of PHN. In terms of safety, no significant difference was noted in the incidence of adverse reactions between high- and low-dose groups.

Totally Robotic Distal Gastrectomy: A Safe and Feasible Minimally Invasive Technique for Gastric Cancer Patients Who Undergo Distal Gastrectomy.

PURPOSES: To explore the safety and feasibility of totally robotic distal gastrectomy (TRDG) for gastric cancer patients who undergo distal gastrectomy. METHODS: Consecutive patients with gastric cancer who underwent TRDG (TRDG group) and robotic-assisted distal gastrectomy (RADG) (RADG group) were systematically reviewed at the Second Xiangya Hospital of Central South University from October 2015 to August 2018. Data were collected and statistically analyzed. RESULTS: A total of 161 consecutive patients were included in this study: 84 cases in the TRDG group and 77 in the RADG group. Clinical characteristics and pathological results were mostly similar in both groups. The TRDG group had a significantly longer anastomotic time (20.6 ± 3.3 vs. 17.5 ± 4.0 min, p ˂ 0.001) but showed no difference in total operating time (167.0 ± 18.0 vs. 162.9 ± 17.6 min, p = 0.159). The postoperative hospitalization in the TRDG group was shorter than that in the RADG group (6.7 ± 1.2 vs. 7.2 ± 1.7 days, p = 0.019). Conversion rate, estimated blood loss, and postoperative complications were similar in both groups. There were no statistical differences in the estimated 2-year disease-free survival and overall survival rate between both groups. CONCLUSIONS: Although our current results need to be verified in further studies, TRDG represents a safe and feasible approach to distal gastrectomy and embodies the theory of minimally invasive surgery.

Robotic Transanal Minimally Invasive Surgery for Rectal Lesions.

Background. Transanal minimally invasive surgery (TAMIS) was developed as a less aggressive alternative treatment for rectal lesions. The purpose of this study was to report the results of robotic TAMIS for such patients. Methods. Patients eligible for TAMIS were operated on using the da Vinci robotic surgical system and GelPOINT Path Transanal Access Platform. Patient demographics, lesion characteristics, perioperative data, complications, and follow-up of all patients were recorded retrospectively. Results. Between March 2015 and August 2018, 24 patients underwent robotic TAMIS by using the da Vinci Si or Xi. The median operative time was 129.6 minutes, and the estimated blood loss was minimal. The mean length of hospital stay was 4.6 days, with no operative complications and no 30-day mortality. There were no statistically significant differences in clinical results and pathological outcomes between the 2 generations of da Vinci systems. Conclusions. With the use of robotic technology, transanal local excision for rectal lesions can be performed with relative ease and safety and can be potentially decreasing the morbidity associated with more aggressive surgical techniques.

Protective effects of Naoxintong capsule alone and in combination with ticagrelor and atorvastatin in rats with Qi deficiency and blood stasis syndrome.

CONTEXT: Naoxintong Capsule (NXT), a Chinese medicine, has been widely used for the treatment of coronary heart disease (CHD) in clinics. OBJECTIVE: This study evaluated the cardioprotective effects of NXT alone and in combination with ticagrelor (TIC) and atorvastatin (ATO). MATERIALS AND METHODS: Qi deficiency and blood stasis rats were established by 8 weeks high fat diet feeding and 16 days exhaustive swimming and randomly divided into seven groups, that is, NXT (250, 500 and 1000 mg/kg/d), TIC (20 mg/kg/d), ATO (8 mg/kg/d), NXT (500 mg/kg/d)+TIC (20 mg/kg/d) and NXT (500 mg/kg/d)+ATO (8 mg/kg/d) group, with oral administration for 12 weeks. The contents of TC, TG, LDL-C, HDL-C, IL-1ß, IL-6, IL-8, TNF-α, AST, ALT, SOD, MDA, CK-MB, LDH, TXA2, PGI2, IgA, IgG, IgM and C3 in serum were measured. RESULTS: NXT + TIC group was significantly superior to the TIC group in decreasing the levels of TC (4.34 vs. 5.54), TG (3.37 vs. 4.66), LDL-C (1.21 vs. 1.35), LDH (4919.71vs. 5367.19) and elevating SOD level (248.54 vs. 192.04). NXT + ATO group was significantly superior to the ATO group in decreasing the levels of AST (195.931 vs. 241.63), ALT (71.26 vs. 83.16), LDH (4690.05 vs. 5285.82), TXA2 (133.73 vs. 158.67), IgG (8.08 vs. 9.80), C3 (2.03 vs. 2.35) and elevating the levels of HDL-C (1.19 vs. 0.91), SOD (241.91vs. 209.49). CONCLUSIONS: The present findings demonstrate that the combined use of NXT with TIC and ATO had better integrated regulating effects than TIC and ATO, respectively. The mechanism of action requires further research.

MicroRNA-146a-5p enhances radiosensitivity in hepatocellular carcinoma through replication protein A3-induced activation of the DNA repair pathway.

Hepatocellular carcinoma (HCC) is known for its high mortality rate worldwide. Based on intensive studies, microRNA (miRNA) expression functions in tumor suppression. Therefore, we aimed to evaluate the contribution of miR-146a-5p to radiosensitivity in HCC through the activation of the DNA damage repair pathway by binding to replication protein A3 (RPA3). First, the limma package of R was performed to differentially analyze HCC expression chip, and regulative miRNA of RPA3 was predicted. Expression of miR-146a-5p, RPA3, and DNA damage repair pathway-related factors in tissues and cells was determined. The effects of radiotherapy on the expression of miR-146a-5p and RPA3 as well as on cell radiosensitivity, proliferation, cell cycle, and apoptosis were also assessed. The results showed that there exists a close correlation between miR-146a and the radiotherapy effect on HCC progression through regulation of RPA3 and the DNA repair pathway. The positive rate of ATM, pCHK2, and Rad51 in HCC tissues was higher when compared with that of the paracancerous tissues. SMMC-7721 and HepG2 cell proliferation were significantly inhibited following 8 Gy 6Mv dose. MiR-146a-5p restrained the expression of RPA3 and promoted the expression of relative genes associated with the DNA repair pathway. In addition, miR-146a-5p overexpression suppresses cell proliferation and enhances radiosensitivity and cell apoptosis in HCC cells. In conclusion, the present study revealed that miR-146a-5p could lead to the restriction of proliferation and the promotion of radiosensitivity and apoptosis in HCC cells through activation of DNA repair pathway and inhibition of RPA3.

Simultaneously Quantitative Analysis of Naringin and Its Major Human Gut Microbial Metabolites Naringenin and 3-(4'-Hydroxyphenyl) Propanoic Acid via Stable Isotope Deuterium-Labeling Coupled with RRLC-MS/MS Method.

Widespread in citrus fruits, naringin, a natural 2,3-dihydroflavonoid, is of particular interest to scientists and has a broad range of beneficial bioactivities to health. Orally administered naringin remains in the gut tract for a relatively long time because of its low bioavailability. Under the metabolism mediated by human gut microbiota, naringin could be an active precursor for derived metabolites to play important physiological roles. However, naringin and its metabolites are hard to accurately quantify due to severe endogenic interference. In this study, an analytical rapid resolution liquid chromatography tandem mass spectrometry (RRLC-MS/MS) method coupled with stable isotope deuterium-labeling is developed and validated to simultaneously quantify naringin as well as its major human gut microbial metabolites naringenin and 3-(4'-hydroxyphenyl) propanoic acid. By eliminating the matrix interferences, this strategy not only confirms naringenin and 3-(4'-hydroxyphenyl) propanoic acid as the predominant metabolites which contribute to the pharmacological effects of naringin but also provides a suitable choice for other flavonoid pharmacokinetics study.

Functional role of a long non-coding RNA LIFR-AS1/miR-29a/TNFAIP3 axis in colorectal cancer resistance to pohotodynamic therapy.

Colorectal Cancer (CRC) is one of the most common digestive system malignant tumors. Recently, PDT has been used as a first-line treatment for colon cancer; however, limited curative effect was obtained due to resistance of CRC to PDT. During the past decades, accumulating CRC-related long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs have been reported to exert diverse functions through various biological processes; their dysregulation might trigger and/or promote the pathological changes. Herein, we performed microarrays analysis to identify dysregulated lncRNAs, miRNAs and mRNAs in PDT-treated HCT116 cells to figure out the lncRNA-miRNA interactions related to the resistance of CRC to PDT treatment, and the downstream mRNA target, as well as the molecular mechanism. We found a total of 1096 lncRNAs dysregulated in PDT-treated CRC HCT116 cells; among them, LIFR-AS1 negatively interacted with miR-29a, one of the dysregulated miRNAs in PDT-treated CRC cells, to affect the resistance of CRC to PDT. LIFR-AS1 knockdown attenuated, whereas miR-29a inhibition enhanced the cellular effect of PDT on HCT116 cell proliferation and apoptosis. Furthermore, among the dysregulated mRNAs, TNFAIP3 was confirmed to be a direct target of miR-29a and exerted a similar effect to LIFR-AS1 on the cellular effects of PDT. In summary, LIFR-AS1 serves as a competitive endogenous RNA (ceRNA) for miR-29a to inhibit its expression and up-regulate downstream target TNFAIP3 expression, finally modulating the resistance of CRC to PDT. We provide an experimental basis for this lncRNA/miRNA/mRNA network being a promising target in CRC resistance to PDT treatment.